Research Summary The United States is facing an opiate epidemic that is spiraling out of control, with a recent CDC report finding that drug overdoses kill one and a half times more people annually than motor vehicle accidents. This epidemic has been driven, in part, by the high prevalence of chronic pain conditions. The interconnected problems of chronic pain and the opiate epidemic are expected to persist and even worsen in the short term. Given these complex and deadly challenges, patients and medical providers are in desperate need of solutions. Simultaneously, the wide availability of medical and recreational cannabis has increased dramatically within the past decade as a result of legalization in 2 states. Data suggest that management of chronic pain is a driving motivation among medical cannabis users, and recent studies suggest that medical cannabis users report cannabis to be more effective at managing pain as compared to opiates. As a result, pain patients are increasingly turning to cannabis as a form of treatment. At the same time, highly respected institutions like the National Academy of Sciences have published systematic reviews indicating that there is substantial evidence that cannabis products are actually effective in the treatment of pain. Despite the burgeoning body of evidence that supports the idea that cannabis may play a helpful role in the chronic pain and opiate epidemic, prospective studies on the effectiveness and safety profile of cannabis as a treatment for reducing opiate use are virtually non-existent in the U.S. The proposed research is timely and would address a glaring gap in the knowledge base in ways that could potentially have an important public health impact. In light of the current legal climate prohibiting a traditional randomized controlled trial with legal market cannabis products, we propose a patient-centered and highly innovative adaptive intervention design to examine the effectiveness of the cannabis products that patients are already using to reduce reliance on opiates. Consistent with federal laws, we will not be involved in the dispensing of the products and we will not direct the administration or dosing of the products. Our overarching aim is to compare three broad classes of orally administered products (i.e., ?edibles?): a THC only product, a product that has a 1:1 THC to CBD ratio, and a CBD only product over the course of 12 weeks in a sample of individuals who want to reduce their opiate use and plan to use cannabis to do so. The primary clinical outcome is opiate use reduction, and the secondary outcome is pain control. We will also conduct acute laboratory sessions in our mobile pharmacology lab to directly examine mechanisms that may mediate the effect of the cannabis products on the clinical outcomes.